1. Field of the Invention
This invention relates to the use of tenidap and the pharmaceutically-acceptable base salts thereof for inhibiting the release of elastase by neutrophils in a mammal. Tenidap and its salts are useful for inhibiting the release of elastase by neutrophils in a mammal, per se, and in treating elastase-mediated diseases and dysfunctions in a mammal. Such elastase-mediated diseases and dysfunctions include, but are not limited to, arteritis, proteinuria and pulmonary emphysema. The use of tenidap and its salts comprises administering an effective amount thereof to a mammal.
2. General Background
Tenidap, 5-chloro-2,3-dihydro-2-oxo-3-(2-thienylcarbonyl)-indole-1-carboxamide, has the structural formula ##STR1## Tenidap, among other 3-substituted-2-oxindole-1-carboxamides are disclosed and claimed in U.S. Pat. No. 4,556,672 which is assigned to the assignee hereof. That patent discloses that those compounds, in addition to being useful as antiinflammatory and analgesic agents, are inhibitors of both cyclooxygenase (CO) and lipoxygenase (LO). The teachings thereof are incorporated herein by reference.
The use of tenidap and its pharmaceutically-accceptable base salts, among certain other 3-substituted-2-oxindole-1-carboxamides, to inhibit interleukin-1 biosynthesis in a mammal and to treat interleukin-1 mediated disorders and dysfunctions is disclosed in U.S. Pat. No. 4,861,794 which is assigned to the assignee hereof.
U.S. Pat. No. 4,853,409, assigned to the assignee hereof, discloses the use of tenidap and its pharmaceutically-acceptable base salts, among certain other 3-substituted-2-oxindole-1-carboxamides, to suppress T-cell function in a mammal and to treat T-cell mediated autoimmune disorders of the systemic or organ specific type.
An anhydrous, crystalline form of the sodium salt of tenidap is disclosed in European Patent Application 277,738, which has been filed in the name of the assignee hereof.
Elastase is a protease which is released by neutrophils in a mammal and mediates certain diseases and dysfunctions. [Janoff, A., American Journal of Pathology 68:579-591 (1972).] Such elastase mediated diseases and dysfunctions include, but are not limited to, arteritis, proteinuria and pulmonary emphysema [Janoff, A., Op. cit. and Johnson, R. J., et al., J. Exp. Med. 168:1169-1174 (1988).]
Until the invention herein, there was no report of use or intent to use tenidap or its salts to inhibit release of elastase by neutrophils in a mammal and to treat elastase-mediated diseases and dysfunctions with such compounds nor any appreciation of their role in such treatments.